Abstract
Systemic lupus erythematosus (SLE) is a complex autoimmune disease of unknown etiology and limited available therapeutic options frustrating both clinicians and patients. However, recent advances in the understanding of disease mechanisms have given rise to numerous studies on specific approaches to SLE treatment. The purpose of this review is to explain the rationale for new treatments and results of the first clinical studies. We will focus on agents which deplete B cells (anti-CD20, anti-CD22), block cytokines (TNF α, Il 6), inhibit B/T cells interaction (CTLA-4Ig, anti-CD40L), or are even expected to reconstruct physiologic immunotolerance. Although preliminary results seemed promising, two randomized clinical trials with rituximab (EXPLORER and LUNAR study) failed to prove efficacy. Data analysis continues to explain the reasons. Trial design, subject population, limitations of the outcome measure instrument and site qualification have been questioned. Future studies are likely to focus on specific organ involvement or treatment combinations with other immunosuppressive agents.
Keywords: B cells, systemic lupus erythematosus, rituximab, epratuzumab, BLyS, LJP 394, anti-cytokine therapy, monoclonal antibodies, clinical trials
Mini-Reviews in Medicinal Chemistry
Title: Target Therapies in Systemic Lupus Erythematosus: Current State of the Art
Volume: 10 Issue: 10
Author(s): E. Wiesik-Szewczyk, J.K. Lacki, W. Feleszko and M. Olesinska
Affiliation:
Keywords: B cells, systemic lupus erythematosus, rituximab, epratuzumab, BLyS, LJP 394, anti-cytokine therapy, monoclonal antibodies, clinical trials
Abstract: Systemic lupus erythematosus (SLE) is a complex autoimmune disease of unknown etiology and limited available therapeutic options frustrating both clinicians and patients. However, recent advances in the understanding of disease mechanisms have given rise to numerous studies on specific approaches to SLE treatment. The purpose of this review is to explain the rationale for new treatments and results of the first clinical studies. We will focus on agents which deplete B cells (anti-CD20, anti-CD22), block cytokines (TNF α, Il 6), inhibit B/T cells interaction (CTLA-4Ig, anti-CD40L), or are even expected to reconstruct physiologic immunotolerance. Although preliminary results seemed promising, two randomized clinical trials with rituximab (EXPLORER and LUNAR study) failed to prove efficacy. Data analysis continues to explain the reasons. Trial design, subject population, limitations of the outcome measure instrument and site qualification have been questioned. Future studies are likely to focus on specific organ involvement or treatment combinations with other immunosuppressive agents.
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Wiesik-Szewczyk E., Lacki J.K., Feleszko W. and Olesinska M., Target Therapies in Systemic Lupus Erythematosus: Current State of the Art, Mini-Reviews in Medicinal Chemistry 2010; 10 (10) . https://dx.doi.org/10.2174/138955710792007187
DOI https://dx.doi.org/10.2174/138955710792007187 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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